Changes in myocardial gene expression associated with β-blocker therapy in patients with chronic heart failure

Abstract

BackgroundThe left ventricular functional recovery by β-blocker therapy is now attributed to time-dependent biologic effects on cardiomyocytes. Methods and resultsTo elucidate the cellular mechanism of these biologic effects, we treated 9 patients with dilated cardiomyopathy for 4 months with β-blockers and examined the gene expressions linked to an improvement of left ventricular ejection fraction (EF). Gene expressions of the biopsied right ventricular endomyocardium were assessed by real-time reverse transcription-polymerase chain reaction. A decrease in β-myosin heavy chain (1.23±0.49 versus 0.86±0.45, P<.05) was observed 4 months after the administration of β-blockers. The expression levels of both sarcoplasmic reticulum Ca2+ ATPase (SERCA) (0.80±0.28 versus 1.39±0.44, P<.01) and phospholamban (PLB) (0.49±0.08 versus 0.88±0.34, P<.05) increased, whereas the expression levels of Na+-Ca2+ exchanger (NCX), β-adrenoreceptor kinase 1, and ryanodine receptor 2 were unchanged. The SERCA/NCX ratio (0.68±0.14 versus 0.96±0.33, P<.05) also increased. The increase in SERCA mRNA expression correlated with the degree of changes in EF (%ΔEF) (r=0.679, P<.05), and none of changes in these genes expression correlated with changes in the plasma brain natriuretic peptide concentration. ConclusionsThe functional recovery resulting from β-blockers may be associated with the restoration of the unfavorable gene expression that controls Ca2+ handlings in the failing heart.